A proposed CMS rule would clarify and tighten how Medicare Drug Price Negotiation applies to fixed combination therapies, potentially affecting lifecycle management strategies used by large oncology brands. Reporting indicates the rule is designed to close an “evergreening” loophole tied to extending patent-protected exclusivity through new formulations, with Keytruda and Opdivo expected to face scrutiny in later negotiation rounds. The rule would modify the Medicare negotiation framework under the Inflation Reduction Act, including the handling of under-the-skin products and whether new formulations can be deselected if biosimilars enter the market. CMS is expected to publish a list of impacted drugs ahead of the first applicable negotiation cycle beginning this year, with further rounds planned. For manufacturers, the update increases regulatory uncertainty around formulation-driven revenue protection and could reshape incentives for next-generation delivery and combination strategies.